guidelines for the submission of a request to include a ......to the pharmacoepidemiology and...

מדינת ישראלSTATE OF ISRAEL

Ministry of Health משרד הבריאות Pharmaceutical Administration אגף הרוקחות

Guidelines for the submission of a request to include a pharmaceutical

product in the national list of health services The National Health Insurance Law, 1994

Date: January 2010 Guideline no. 53 version no: 8

___________________________________________________________________________ .Tel. 972-2-5681200 29 Rivka Str: טל 2קומה 29רבקה ' רח FAX 972-2-6725820 P.O.B. 1176: פקס 1176. ד.ת

www.health.gov.il/drugs Jerusalem 91010 91010ירושלים

1. General instructions for submission of a request to include a pharmaceutical product in the health services “basket”:

1.1 A request to include a pharmaceutical product in the national list of health

services (“basket”) will include a comprehensive data file which will be submitted to the Pharmacoepidemiology and Pharmacoeconomics Department at the Pharmaceutical Administration of the Ministry of Health, according to the guidelines detailed herewith.

1.2 One data file will be submitted for all dosage forms, for all strengths and

approved indications of the pharmaceutical product.

1.3 The data file will be submitted by the appointed pharmacist of the license holder of the pharmaceutical product.

1.4 All data and references will be in Hebrew and/or English. Official documents

should be submitted in their original language. If the submission is only in English please attach a Hebrew translation of the summaries of parts II and III (see section 3.1.6 and 3.1.7).

1.5 Submission of the file will be submitted also on electronic media.

1.6 Inclusion of a pharmaceutical product in the health services basket is done on the

basis of a predefined budget, according to decisions made by the public committee for the update of the basket appointed by the Minister of Health. The Pharmacoepidemiology and Pharmacoeconomics Department will consider each application and after assessment will pass its recommendations to the appropriate authorities. Therefore, a complete and detailed request does not guarantee the requested pharmaceutical product to be considered by the appropriate authorities for inclusion in the health services basket or implicates the Ministry of Health in any possible way. However, the process of decision making is based on the data submitted in the request and hence the great importance of the request’s content.

1.7 These guidelines contain a number of compulsory paragraphs (designated with an

asterisk). The data appearing in these paragraphs is of crucial importance in the decision making process.

1.8 The data submitted will be processed by the Pharmacoepidemiology and

Pharmacoeconomics Department and presented to the public committee in a uniform format.








2. Structure of the data file:

2.1 A request to include a pharmaceutical product in the national health services basket will be composed of three parts to be submitted according to section 3 of these guidelines: Part I: Request forms and documents pertaining to details of the pharmaceutical product and a detailed summary of the data presented in parts II and III. Part II: Clinical and epidemiological data. Part III: Clinical-Economic evaluation.

2.2 The request will be submitted in a single binder separated by dividers.

2.3 On the back of the binder the name of the pharmaceutical product and the license

holder’s name, will be stated. 3. Dossier elements:

3.1 Part A - General: 3.1.1 Index

3.1.2 General description of the product (Form 1) (Appendix A).

*3.1.3 One page summary of the disease’s nature and the pharmaceutical

product’s relative benefits in comparison to the therapeutic alternatives that are included in the basket.

*3.1.4 The product’s registration certificate (including full indications). *3.1.5 Product monograph (if there is none - Full prescribing information

(Physician leaflet)). 3.1.6 Detailed summary of the data presented in part II.

3.1.7 Detailed summary of the data presented in part III.

*3.1.8 An affidavit of the product’s price in Israel (Form 2) (Appendix B) - The

product’s price in Israel is defined as the selling price for the Sick Funds if the product is included in the basket.








3.2 Part II – Clinical and Epidemiological data:

3.2.1 Clinical-Pharmacological profile:

Briefly describe the general pharmacological profile of the pharmaceutical product’s therapeutic class and the specific pharmaceutical product, according to the following points:

3.2.1.1 The pharmaceutical product:

- Other countries in which the product is registered and the registered indications in each country (if different from the registered name in Israel)

- Recommended and commonly used treatment regimens with the product, including expected length of treatment.

- If the pharmaceutical product is indicated for use in combination with other pharmaceutical products, these combinations should be detailed, together with the required dosages.

- Summary of the adverse effects reported as part of the product’s post marketing surveillance (only the summary of the last PSUR).

- Significant adverse effects, precautions / warnings and drug-drug interactions.

- Which changes have been made, if any, after receiving the marketing authorization (warnings, side effects, etc.)

- If the pharmaceutical product is being used in Israel under regulation 29 a(3), describe for which indications and how many patients are treated according to this approval.

- Detail other indications currently under research or any off label use of the pharmaceutical product, including all approved indications abroad (please state date of approval for each indication).

3.2.1.2 The Therapeutic class:

- Name of the therapeutic class and its classification according to the ATC classification system.

- Major pharmacological action of pharmaceutical products in this class.

- The rationale for using pharmaceutical products in this class.








3.2.1.3 Alternative treatment options: What are the major treatment options (drug and non-drug) currently existing in Israel for the same indication. For each treatment option specify if it is included in the basket, or not. For each alternative medicinal treatment option summarize according to the following points: Brief pharmacological profile; mechanism of action; rationale for use of pharmaceutical products; efficacy and major side effects. Please emphasize the aspects that differ significantly from the proposed pharmaceutical product. It is recommended that the data presented will be in a tabular form.

3.2.1.4 Summarize briefly results from relevant clinical trials pertaining to

the pharmaceutical product’s efficacy for the relevant indication. Preferably use comparative studies in which the proposed pharmaceutical product is compared to other treatment options used for the same indication (see explanation in paragraph 3.2.5).

3.2.1.5 Attach any official treatment guideline/protocol for the requested

indication/s (in Israel and / or other countries) in which the proposed product is part of. Highlight the relevant part concerning the proposed product.

3.2.1.6 State how does the treatment with the proposed pharmaceutical

product influence patient survival (percentage or in “months of living”)

3.2.1.7 State how does the treatment with the proposed pharmaceutical

product influence the patient’s quality of life (if available list studies and data such as QALY)

3.2.1.8 Briefly summarize studies assessing the clinical outcomes of the

treatment, such as indices of morbidity, mortality, quality of life, aspects of cost effectiveness and more.








*3.2.1.9 Expert report:

3.2.1.9.1 An expert report by at least one physician specializing in the field the pharmaceutical product is indicated for, should be submitted.

3.2.1.9.2 The expert report must be based on all the data

presented in the request and refer to the following points: - Efficacy and importance of the pharmaceutical

product in comparison to alternative treatment for the same indication.

- Personal experience with the pharmaceutical product. - Definition of the pharmaceutical product’s place in

therapy (for example second/third line, specific patient groups to benefit the most from the treatment, etc.)

3.2.1.9.3 At the end of the report the following signed statement

will appear: “I am a physician, qualified to give this expert report on behalf of the requesting party. I give this expert report in support of a request to include this pharmaceutical product in the National Health Services list, according to the National Health Insurance Law, based on the entire file presented before me and my personal experience. Herewith are details of my status and education: I hereby declare that this is my name, that is my signature and the content of my expert report is true.”

3.2.1.9.4 Each expert report must be accompanied by a signed

form of full disclosure (טופס גילוי נאות) (See appendix C)

3.2.1.9.5 Expert reports that do not meet with the above

mentioned criteria will not be taken under consideration.








3.2.2 Pharmacoepidemiological data

*3.2.2.1 Summarize briefly the disease state to which the pharmaceutical product is indicated for (pathophysiology and clinical course) and the typical gradual treatment regimen.

*3.2.2.2 The disease’s epidemiology:

- Prevalence: number of patients in Israel. - Incidence: number of new patients each year in Israel. Include, where available, incidence and prevalence data from other western world countries.

*3.2.2.3 What is the market size (number of patients treated currently for

the specific disease state) and its distribution for each of the treatment options detailed in section 3.2.1.3 (Use market surveys data, IMS, etc).

*3.2.2.4 Cite the Israeli sales figures of the requested pharmaceutical

product from the last three years.

3.2.2.5 By how much is the target population expected to increase within the next three years following inclusion of the proposed pharmaceutical product in the basket.

*3.2.2.6 Is the requested pharmaceutical product included in a Sick Fund’s

formulary in Israel (If so, in which Sick Fund, date of inclusion in the formulary, rate of co-payment and type of insurance).

*3.2.2.7 Is the requested pharmaceutical product included in a formulary

of a public insurer in other countries (state name of country and rates of co-payment).








3.2.3 The new treatment equilibrium:

3.2.3.1 As part of the treatment regimen what is the requested place of the pharmaceutical product.

3.2.3.2 How many patients are expected to switch from their current

treatment to the proposed pharmaceutical product (based on clinical and/or economic considerations) after inclusion of the proposed pharmaceutical product in the health basket.

*3.2.3.3 Characteristics of the specific patient population which will

benefit the most from receiving treatment with the proposed pharmaceutical product.

3.2.3.4 After inclusion of the proposed pharmaceutical product in the

health basket what is expected new market share for each treatment option (what percentage of the patients will be treated with each treatment option).

3.2.3.5 Is the market expected to grow after inclusion of the proposed

pharmaceutical product in the health basket (will the number of treated patients increase)? If so, by how much.

3.2.4 Pharmaceutical Products that will bear no added cost to the basket

according to the dossier submitter’s assessment: Attached to the full dossier will be a segment detailing the arguments as to why the inclusion of the proposed pharmaceutical product will bear no added cost to the health services basket. This part will be based on a comparison to therapeutic alternatives that are included in the basket. In such a case, submission of a full dossier is necessary to ensure discussion of the requested pharmaceutical product as any other proposed product, in case there will not be an agreement as to the product not adding costs to the basket








3.2.5. Supporting clinical information: *3.2.5.1 Attach a printout of the previous year’s abstracts.

3.2.5.2 For any data / research / trial cited it is mandatory to attach the original paper / source. Moreover for each trial summarize the following data elements:

3.2.5.2.1 Name of trial. 3.2.5.2.2 Location and trial date. 3.2.5.2.3 Publication citation/s. 3.2.5.2.4 Trial design, randomization and blinding procedures.

3.2.5.2.5 Inclusion and exclusion criteria. 3.2.5.2.6 Treatments to which the proposed pharmaceutical

product was compared (including placebo). 3.2.5.2.7 Treatment and dosage regimens

3.2.5.2.8 Sample characteristics: demographics, sample size, disease severity and comorbidities.

3.2.5.2.9 Patient follow-up procedures: if intention to treat, were drop-outs followed ?

3.2.5.2.10 Clinical and other outcomes measured and their statistical significance.

3.2.5.2.11 Compliance behavior. 3.2.5.2.12 Concordance of the achieved outcomes in the trial’s

sample and the actual expected outcomes in the target population (considering differences of treatment protocol, treatment populations, comorbidities, compliance, follow-up, etc.). If such a difference exists, propose a model to link the trial’s results with the expected outcomes in Israel while detailing the justification to the model’s assumptions.

3.2.5.3 If meta analyses have been undertaken, these should be summarized

with particular emphasis on the inclusion criteria for studies analyzed. Justify the relevance of the analysis to the target population.








3.2.5.4 Where a retrospective study has been undertaken (utilizing pharmacy and medical claims databases) the study should be summarized and should include, in addition to the above information, the research question or hypothesis tested, rationale for the study design, choice of data source, techniques used to assess data quality, rationale for chosen statistical or econometric procedure and techniques used to avoid issues such as selection bias.

3.3 Part III: Economic evaluation

3.3.1 An economic evaluation of the proposed pharmaceutical product must be

submitted (See instructions in Appendix D: Instructions for performing an economic assessment).

3.3.2 An economic evaluation conducted abroad should be adapted to Israeli

settings. In such cases the request will include both evaluations.

3.3.3 The summary of the economic evaluation will be performed according to the following: 3.3.3.1 Estimated costs will be given in NIS and according to the

following: 3.3.3.1.1 Cost of treatement to the patient with the

proposed technology. 3.3.3.1.2 Cost of treatment to the patient with the

alternative treatment. 3.3.3.1.3 Total additional cost (number of patients X

additional cost per patient)

3.3.3.2 Estimated utilities will be given in QALY and according to the following:

3.3.3.2.1 Utility per patient with the proposed technology. 3.3.3.2.2 Utilty per patient with the alternative treatment.

3.3.3.2.3 Additional utility per patient (the difference between the utilities)

3.3.3.3 The incremental cost per QALY (in NIS)

The additional cost per patient divided by the additional utility per patient.








Appendix A

Form 1

General description of the pharmaceutical product Name of the product: __________________________ Registered dosage form in Israel (including dosage forms, strength/concentration, package type and quantity/size and registration number): 1. __________________________________________________________________________ 2. __________________________________________________________________________ Active ingredients (Generic names) and their quantity in dosing units: 1. __________________________________________________________________________ 2. __________________________________________________________________________ Registered indications in Israel (including date of approval of each indication): 1. __________________________________________________________________________ 2. __________________________________________________________________________ General: Name of license holder: ____________________________________________________________________________ License holder’s address (in Israel and abroad): ______________________________________ ____________________________________________________________________________ ___________________________________________________________________________ Name of the appointed pharmacist: _______________________________________________ Pharmacist’s License number: ___________________ Affidavit: To my knowledge and professional responsibility, I, the undersigned, declare herewith that all the data submitted in this request are correct. ________________________ _______________________________ ______________ Name of the appointed Stamp and signature of the appointed Date Pharmacist pharmacist








Appendix B

Form 2

Affidavit of the product's price ISRAEL Institutional Price – the selling price to the Sick Funds if the product will be included in the basket Dosage forms

Strength

Package type and quantity

Price per package (for institutions)*

Number of estimated patients








Global: Current institutional price in The Netherlands, France, Belgium, Germany, Great Britain, Spain, Portugal, Hungary and Poland (Fill the form seperately for each country):

Country

Dosage forms

Strength

Package type and quantity

Price per package (for institutions)*

Number of estimated patients

________________________ _______________________________ ______________ Name of the license holder Stamp and signature of the license Date or a corporate manager who holder or the corporate manager who is the license holder is the license holder








Appendix C

Recommendation for the health services basket – Full disclosure form

|__|__|/|__|__|/|__|__|: תאריך

___________, מתוצרת חברת _______ ______דעתי המקצועית ביחס לתכשיר חוותובכוונתי לתת הואילהמייעצת לשר הבריאות בכל הקשור להכללת , הציבורית להרחבת סל שרותי הבריאות הועדהלשם הבאתה בפני

:כלהלןהריני מצהיר , ביטוח בריאות ממלכתי חדשות בסל שרותי הבריאות שלפי חוק טכנולוגיות אינני , במישרין או בעקיפין, תמורת תשלום, אינני יועץ לה_________, כי איני עובד בחברה לאשר הריני . 1

או קשור אליה בקשר אחר המונע ממני לתת חוות דעתי בצורה , במוסדותיהממלא תפקיד או נושא משרה קשוראינני קשור לחברה בכל קשר אחר ולא הייתי . ה חשש לניגוד ענייניםאו בצורה המעל/ואובייקטיבית

.לתכשיר אחר בזיקהואם , אם בזיקה לתכשיר הנדון, גם בעבר, באחת או יותר מהזיקות המפורטות, עמה

מאשר מאשר לא לעיל והן מפורטות 1מתקיימת אצלי זיקה אחת או יותר מן הזיקות המפורטות לסעיף הריני להודיע כי .2

:להלן

לא / כן: או מחקר אחר ביחס לתכשיר הנדון, השתתפתי במחקר קליני במימון החברה ביחס לתכשיר הנדון

ה שקדמה לחתימ, מחקר שטרם הסתיים בתקופת שלוש השנים( במימון החברהאחר השתתפתי במחקר קליני ) _____________________________פרט מועד תחילת המחקר וסיומו: אם כן(, לא / כן –) על טופס זה

לא / כן, בשלוש השנים שקדמו לחתימת טופס זה תי בכנס במימון החברהיהרצ

לא / כן: בשלוש השנים שקדמו לחתימת טופס זה, נסעתי על חשבון החברה לכנס מקצועי

לא / כן: בשלוש השנים שקדמו לחתימת טופס זה, ל החברהשימשתי כיועץ ש

לא / כן: בשלוש השנים שקדמו לחתימת טופס זה, עבדתי בחברה

פרט( אחר ( ____________________________________________________________________ _____________________________________________________________________________

____________________________________________________________________________ או יותר באחתעימם אני מצוי אחריםלאשר כי לא ידוע לי על זיקת תחרות בין גורם או גורמים הריני .3

, בסל שירותי הבריאות הכללתוהנדון או לשאלת לתכשירביחס , לבין החברה, מהזיקות המפורטות לעיל .כאמורמחשש לניגוד עניינים , זאתהמונעת ממני ליתן חוות דעתי

מאשר מאשר לא

הזיקות אינו בגדר זיקה מן, כל כולו מתפקידי כעובד מדינה או כעובד קופה הנובע, עם חברה מסחרית קשר .4 או העובד ממלא בה/והקופה הינה בעלת מניות בחברה –לעניין עובד קופה –אלא אם כן , 1בסעיף מפורטות

או מתוקף , הם מטעם הקופה המשרהאף אם מילוי התפקיד או , בשכר או שלא בשכר, תפקיד או מישרה .תפקידו של העובד בה

הוא מידע שעל משרד הבריאות לגלותו לכל דורש לפי , בו על הפרטים הנכללים, ידוע לי כי הטופס שמילאתי .5 ).1998-ח"תשנ(חוק חופש המידע

____________________:חתימה _ _________________________________: שם








Appendix D

Instructions for performing an economic assessment

The economic evaluation of medical technologies includes comparative analysis between alternatives in

terms of costs and outcomes, and seeks to provide an objective and systematic method to improve the

prioritizing process among decision-makers.

The assessment of the submitted material and the economic evaluation are conducted by a multi-

disciplinary team of experts. The team examines whether the request fulfills the criteria for assessment

and demands additional information, as needed.

The economic evaluation form provides a unified format to enable comparison between all medical

technologies considered for inclusion in the Israeli National List of Health Services (INLHS)

The principles of the Israeli model upon which the guidelines are based are:

• The perspective adopted on benefits is of the health care system

• The perspective adopted on costs is that of the supplier (Ministry of Health, Health Management

Organizations)

• The preferred comparators are standard-of-care technologies included in the INLHS

• The methods of economic evaluation should be Cost-Utility analysis

• Outcomes will be expressed in QALYs

• The costs are the direct medical costs for the supplier and consumer

• Time horizon for costs and outcomes will be defined for each comparison separately in such a way as to

reflect the course of the disease and the effects of the interventions

• Sensitivity analyses should be performed as needed

• Discounts will be made according to the time horizon, and the discount percentage will be 3%








Guidelines for completion of the economic evaluation form for health technologies:

The guidelines refer to all information in the economic evaluation form. The guidelines describe the

necessary data and provide examples as needed.

The request form is a stand-alone document, and all data must be presented and submitted according to

instructions provided in these guidelines.

General guidelines:

1. The applicant is responsible for providing current, relevant and unbiased information, supported by

acceptable and accessible scientific sources, in order to allow the reviewers to perform the necessary

analyses and make recommendation accordingly.

2. All parts of the form must be completed according to the type of technology. If certain parts cannot be

completed, the applicant must provide detailed justification.

3. Additional documents, must be relevant and justified, but do not replace the formal form.

4. All data must be supported by documentation.

5. Data sources must be scientifically accepted and available for assessment and should be submitted as

attached documents.

6. Decision trees or other models relevant to the analysis should be included








The economic evaluation report is composed of 5 sections:

1. Title: contains general data, including the name or description of the technology, the name of the

manufacturer or company, details of the person conducting the economic evaluation and of a contact

person.

2. General description of the submitted technology: the purpose of this section is to provide general details

of the submitted technology, the health condition and indication for use, clinical guidelines' references,

treatment regimen, and target population

3. Description of comparator and comparative effectiveness: this part should describe the comparator used

in the economic evaluation (name and whether it is included in the INLHS), the sources for effectiveness

comparisons (complete references and characteristics of studies) and the endpoints compared.

4. Comparison of costs: this section should present the data used for calculation of cost for the submitted

technology and comparator (including references for pricing) as well as any other costs added or saved

due to increase or decrease use of other technologies or services.

5. Results of the economic evaluation: this section should contain a clear and concise summary of the

main assumptions and parameters upon which the economic evaluation is based and the model used (if

any). The results should include the costs of the submitted technology and comparator and the incremental

cost (including discounting), the benefits (in QALYs) of the submitted technology and comparator and the

incremental benefit (including discounting) and the incremental cost-effectiveness ratio (additional cost

per additional QALY). Sensitivity analyses should be also included.








Section 1- Title

The opening page of the request form includes:

• Proprietary (trade) name of the technology, proper name or description of the technology and

the name of the manufacturer or company.

• Name, title and e-mail of the applicant.

• Contact person, including name, title, address, phone number, fax and e-mail. The contact

person need not be the applicant, but should be able to provide official responses to queries.

• The name and contact details of the person conducting the economic evaluation

Section 2- general description of the submitted technology:

This section includes the following data (if a data is considered not-relevant, it should be noted and

explained).

Condition - primary disease or condition.

Requested indication - the indication requested for inclusion, including place in the therapeutic

sequence.

References for clinical guidelines - acceptable references include guidelines of professional

associations, national institutes and scientific publications. References must be provided.

Context of use - full hospitalization, day hospitalization, outpatient clinic, primary care clinic,

home use

Therapeutic regimen - description of treatment regimen, including duration of treatment.

Target population age - indicate the average age of the intended target population.

Contraindication, precautions and warnings - if exists.








Section 3- Description of comparator and comparative effectiveness.

Description of comparator

Comparators are other technologies used for exactly the same indication.

Comparisons with standard-of-care comparators included in the INLHS are preferred. If no such

comparison is made, the applicant must supply an appropriate explanation. If more than one technology

exists, the applicant may choose with which to compare.

Comparators not in the INLHS are acceptable if there are no alternative in the INLHS, or in addition to

one.

If there are no comparators (either in the INLHS or not), the technology will be compared to "do nothing",

based on data regarding the costs and outcomes of not intervening.

Description and explanation regarding characteristics of sources for outcome comparison:

Clinical trials or studies, where the primary endpoint is the direct clinical outcome used for comparison,

are preferred. If no such trials or studies exist, clinical trials in which the secondary end points are the

outcome used for comparison are acceptable.

The end-point variable may be a direct clinical outcome (e.g. mortality, survival, incidence of disease,

functional performance, quality of life etc.) or a surrogate measure (e.g. change in blood pressure,

hemoglobin A1C, FEV1, etc.). When a surrogate measure is used, the relation with direct clinical

outcomes must be established.

The outcome presented should be accompanied by confidence interval, unless it is not specified in the

cited trial. For any comparison the statistical significance level must be given.

When there are several studies comparing the two technologies, it is preferable to use for the comparison

the most recent ones and/or the ones with the largest study population or is most appropriate for the Israeli

population and setting.

If the study was designed to assess differences in safety, safety should be regarded as the primary endpoint.








The comparison between the technologies must be based on accepted scientific sources and be appropriate

to the submitted indications and outcomes compared.

Study description should be provided according to type of the study/trial used in the comparison, as follow:

For clinical (interventional) trials, the following data should be presented (Table 1a):

• Allocation

• Blinding

• Control

• Assignment

• Study Population- includes definition of the disease/condition and inclusion and exclusion criteria.

• Primary outcome measure

• Secondary outcome measures- include only those with statistically significant differences.

• Length of follow-up

• Comparative safety- only if there were statistically significant safety differences in the adverse events

profile between the two technologies.

For non-clinical-trials studies, the following data should be presented (Table 1b):

• Study Design

• Study Population

• Outcome measures

• Length of follow-up

• Comparative safety- only if there were statistically significant safety differences in the adverse events

profile between the two technologies.








Comparison of outcomes:

The clinical outcomes compared will be based only on the references described in the earlier part of the

section (see Table 1). The comparison between the technologies' outcomes (submitted vs. comparator) will

be presented by means of a table detailing the endpoints used to assess the benefit and the benefit in

numerical value with confidence intervals.

These results will serve as a basis for the calculations of QALYs used in the model in section 5.

Table 1

a. Example of presentation of characteristics of a cited clinical trial

randomized controlled trial Allocation: double blind Blinding: active Control: parallel Assignment : Colorectal cancer patients with bone and/or liver metastases, between the ages 45-85, with no CNS metastases and with no significant coronary heart disease.

Study population:

Overall survival Primary outcome measures : Tumor response rate Progression-free survival

Secondary outcome measures :

2 years Length of follow-up : No significant differences Comparative safety :

b. Example of presentation of characteristics of a cited non-clinical trial

Prospective cohort study Study type: Colorectal cancer patients with bone and/or liver metastases, between the ages 45-85, with no CNS metastases and with no significant coronary heart disease.

Study population :

Overall survival Outcome measures : 2 years Length of follow-up : No significant differences Comparative safety :








Section 4: Cost comparison between technologies.

General principles for cost calculation:

• Cost is presented in current New Israeli Shekels (NIS) values.

• The cost is the direct and indirect medical cost

• The dosing, schedule and duration of treatment are based on standard clinical guidelines.

• If use of the new technology requires or spares spending on other medical technologies, these costs

should be included in the calculation.

In calculation of costs, the costs of each of the two technologies (submitted and comparator) should be

presented, including, as needed, the numbers of units per package and/or per year. The source of pricing of

the technologies should be clearly specified.

If the use of the new technology will require the use of additional medical technologies, or, alternatively,

will spare the use of other medical technologies, this information (costs) should be included in the

calculation.

These additional costs include, but are not limited to:

• Drugs

• Medical devices/ equipment

• Tests- laboratory test and imaging, both as pre-evaluation and as follow-up.

• Clinical examinations- include examinations by both primary care physicians and specialists, as pre-

evaluation and as follow-up.

• Hospitalization

• Medical/ surgical procedures

If there is a need for a one-time expenditure, such as infrastructure or training, this cost should be

presented, but it would not be included in the economic evaluation.








Section 5: Results of economic evaluation.

How to calculate quality adjusted life years (QALYs):

The concept behind QALYs is based on the fact that the outcome of an intervention must affect at least

one out of two components, the quantity of life and the quality of life. QALYs is an arithmetic product to

assess the clinical benefit of an intervention by multiplying the value of the health-related quality of life

(HRQoL) - utility by the length of time (in years) in a particular health state - survival. Utilities are

cardinal values describing the individual's preferences for different health states.

All outcomes compared should be translated into QALYs. This can be done by calculating the effect of

the clinical outcomes of the studies on HRQoL and survival.

This translation may be based on medical literature or on professional opinion.

The following site may be useful for determination of utilities:

https://research.tufts-nemc.org/cear/default.aspx

It is recommended to use values from populations similar to that of Israel.

The utilities should be age and gender-adjusted according to table 2.

The economic evaluation:

This section should describe the model used for the economic evaluation, and its main results. The model

itself (as a computerized file such as Excel, TreeAge etc,) should be sent directly by E-mail to

[email protected].

This description should include the model assumptions, HRQoL weights (utilities), time horizons etc. If

the model has a time horizon of over 1 year, a 3% annual discounting should be used for both costs and

benefits.

If a model prepared for another country is used, adjustment should be made, and specified, to ensure

appropriateness to Israel. These adjustments apply to differences in treatment management as well as the

different pricing of drugs and services. Simple currency conversion at exchange rates is not considered

sufficient adjustment.

https://research.tufts-nemc.org/cear/default.aspx�

mailto:[email protected]�








Both costs, relevant costs from section 4 and costs used in the model should be itemized.

The results should include the following:

Cost per patient treated with the submitted technology

Cost per patient treated with the comparator

Difference in costs

Benefit per patient treated with the submitted technology in QALYs

Benefit per patient treated with the comparator in QALYs

Difference in benefits in QALYs

Incremental cost-utility ratio

Sensitivity analyses

Sensitivity analyses examine the effects of the different parameters on the results of the economic

evaluation. Sensitivity analyses should be performed for both the costs and benefits, and the parameters

examined specified. The range of values used in the sensitivity analyses may be based on the results of

studies (reported confidence intervals) or on clinical judgment. Parameters found to have significant

effects must be specified clearly, along with their implications on the meaning of the results of the

economic evaluation.

Table 2: age adjustments for utilities. Factor - both

Factor - female

Factor - male

AGE Factor - both

Factor - female

Factor - male

AGE

0.828264 0.8216 0.8350 50 0.99325 0.9935 0.9930 0 0.823549 0.8165 0.8306 51 0.992334 0.9928 0.9918 1 0.82149 0.8162 0.8268 52 0.991417 0.9922 0.9907 2 0.816618 0.8109 0.8224 53 0.990501 0.9915 0.9892 3 0.811745 0.8056 0.8179 54 0.989584 0.9908 0.9883 4 0.805198 0.7986 0.8118 55 0.988668 0.9902 0.9872 5 0.800302 0.7933 0.8073 56 0.987752 0.9895 0.9860 6 0.793604 0.7838 0.8035 57 0.986835 0.9888 0.9848 7 0.789000 0.7788 0.7992 58 0.985919 0.9882 0.9837 8 0.784395 0.7739 0.7949 59 0.985002 0.9875 0.9825 9 0.778292 0.7675 0.7890 60 0.984086 0.9868 0.9813 10








Factor - both

Factor - female

Factor - male

AGE Factor - both

Factor - female

Factor - male

AGE

0.773806 0.7628 0.7849 61 0.98317 0.9862 0.9802 11 0.76972 0.7595 0.7800 62 0.982253 0.9855 0.9790 12 0.765235 0.7546 0.7759 63 0.981337 0.9849 0.9778 13 0.760751 0.7497 0.7718 64 0.98042 0.9842 0.9767 14 0.754237 0.7428 0.7657 65 0.979504 0.9835 0.9755 15 0.749636 0.7377 0.7616 66 0.978588 0.9829 0.9743 16 0.744436 0.7327 0.7562 67 0.977671 0.9822 0.9732 17 0.740299 0.7281 0.7525 68 0.976755 0.9815 0.9720 18 0.736162 0.7235 0.7489 69 0.975838 0.9809 0.9708 19 0.729537 0.7165 0.7426 70 0.974922 0.9802 0.9696 20 0.725038 0.7113 0.7388 71 0.970182 0.9751 0.9653 21 0.72099 0.7063 0.7356 72 0.975041 0.9760 0.9741 22 0.716899 0.7021 0.7317 73 0.969981 0.9706 0.9693 23 0.712958 0.6980 0.7280 74 0.96492 0.9653 0.9645 24 0.706303 0.6899 0.7227 75 0.960297 0.9598 0.9608 25 0.701987 0.6858 0.7182 76 0.955219 0.9544 0.9560 26 0.699211 0.6824 0.7160 77 0.956169 0.9578 0.9546 27 0.69586 0.6797 0.7121 78 0.950874 0.9521 0.9496 28 0.692661 0.6763 0.7090 79 0.945579 0.9465 0.9447 29 0.687211 0.6696 0.7049 80 0.939796 0.9405 0.9391 30 0.68126 0.6599 0.7026 81 0.934524 0.9349 0.9342 31 0.684122 0.6679 0.7003 82 0.924046 0.9219 0.9262 32 0.6793 0.6621 0.6965 83 0.918978 0.9166 0.9214 33 0.675095 0.6577 0.6925 84 0.913911 0.9113 0.9166 34 0.669184 0.6497 0.6886 85 0.908338 0.9051 0.9116 35 0.665316 0.6456 0.6850 86 0.903295 0.8998 0.9068 36 0.66056 0.6401 0.6810 87 0.902389 0.8998 0.9050 37 0.656398 0.6351 0.6777 88 0.89714 0.8942 0.9001 38 0.657663 0.6381 0.6772 89 0.891916 0.8887 0.8951 39 0.642708 0.6204 0.6650 90 0.885018 0.8817 0.8883 40 0.639945 0.6171 0.6628 91 0.87989 0.8763 0.8835 41 0.636797 0.6133 0.6603 92 0.873776 0.8692 0.8783 42 0.632945 0.6090 0.6569 93 0.868695 0.8639 0.8735 43 0.627472 0.6033 0.6516 94 0.863614 0.8585 0.8687 44 0.624039 0.5998 0.6483 95 0.856905 0.8521 0.8617 45 0.61839 0.5926 0.6442 96 0.851847 0.8468 0.8569 46 0.61375 0.5878 0.6397 97 0.844342 0.8382 0.8504 47 0.609783 0.5834 0.6362 98 0.839506 0.8331 0.8459 48 0.60454 0.5775 0.6316 99 0.83467 0.8280 0.8414 49

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